Multidrug dissolvable microneedle patch for the treatment of recurrent oral ulcer

Recurrent oral ulcer is a painful oral mucosal disorder that affects 20%of the world’s population.The lack of a radical cure due to its unknown underlying cause calls for innovative symptomatic treatments.This work reports a hyaluronic acid-based dissolvablemicroneedle patch(ROUMNpatch,short for recurrent oral ulcer microneedle)loaded with dexamethasone acetate,vitamin C and tetracaine hydrochloride for the treatment of recurrent oral ulcers.The ROUMN patch shows enhancement in both the anti-inflammatory effect elicited by dexamethasone and the pro-proliferation effect of vitamin C.In vitro experiments show that ROUMN has a higher efficiency in suppressing lipopolysaccharide(LPS)-induced interleukin-6(IL-6)expression than dexamethasone alone.Cell proliferation and migrationwere also significantly promoted byROUMNcompared to vitamin C alone.The healing-promoting effect of ROUMN was also verified in vivo using an acetic acid-cauterized oral ulcer model in rats.ROUMN as a treatment accelerated the healing process of oral ulcers,shortening the total healing time to 5 days compared with the 7 days required by treatment using watermelon frost,a commonly used over-the-counter(OTC)drug for oral ulcers.The rapid dissolution of the hyaluronic acid-based microneedles and the superior healing-promoting effect of the drug combination could lead to a broad application prospect of the ROUMN patch in the treatment of recurrent oral ulcers.

Test Case Analysis Application of Jiawei-yinhuo Soup the Treatment of Recurrent Oral Ulceration

Recurrent oral ulceration,which is small but not easy to cure,seriously affects the quality of life of the patients.This paper analyzes professor Wang Xiaoyan's application of Yinhuotanghuacai to treat oral ulcer with floating of yang in deficiency condition,which can significantly improve the clinical symptoms of patients and improve the quality of life of patients.

Metabolomics characterization of Qingwei San on oral ulcer in db/db mice with stomach heat pattern

Objective:To characterize the effects of Qingwei San(QWS)on diabetic oral ulcer(OU)mice with stomach heat pattern through metabolomic analysis.Methods:A stomach heat pattern mouse model was established by treating C57BLKS/J Leprdb/db(db/db)mice with dried Zingiber officinale Rosc.rhizome(Z.officinale,Gan Jiang)decoction by gavage.All model mice had blood glucose levels of≥11.1 m M.Subsequently,OU was induced by Na OH cauterization.After 1 week of administration of QWS,non-targeted metabolomic analysis of serum was conducted using ultra high performance liquid chromatography coupled with mass spectrometry(UHPLC-MS/MS).Results:The non-targeted metabolomics results indicated that tryptophan metabolism,2-oxocarboxylic acid metabolism,serotonergic synapses,amino sugar and nucleotide sugar metabolism,and amino acid biosynthesis were involved in the therapeutic effects of QWS,with tryptophan metabolism playing a predominant role.Conclusion:QWS treatment can significantly improve the pathological status of diabetic OU mice with stomach heat pattern.QWS may regulate the release of inflammatory factors through the tryptophan metabolism pathway.

Experimental Study of Emilia Sonchifolia Combined with Coptidis Rhizoma for the Prevention and Treatment of Oral Ulcer

Objective: This paper aims to investigate the therapeutic effect of the combination of Emilia Sonchifolia and Coptidis Rhizoma on oral ulcer rats. Methods: 36 SD rats of half male and half female were kept for 7 days, and 6 rats among them were selected as normal group by random sampling method, and the rest rats were randomly divided into model group, positive control group, Emilia Sonchifolia group, Coptidis Rhizoma group and combined group after the establishment of oral ulcer model. The normal group and model group were given blank film, the positive control group was given Guilin Watermelon Frost, and the Emilia Sonchifolia group, Coptidis Rhizoma group and combined group were given the corresponding oral film, which was administered to the ulcer for 7 days continuously, 2 times per day. The healing of oral ulcer was assessed at the end of the last day of administration, and the ulcer area was calculated on the 1st, 3rd, 5th and 7th days after successful modeling, and the serum levels of IL-2 and TNF-α in rats were detected by Emilia Sonchifolia. Results: The grading of ulcer healing in the positive control group and the combined group was better than the other groups, and the difference was statistically significant when compared with the model group (p Coptidis Rhizoma group, Emilia Sonchifolia group, combined group and positive control group was smaller than that in the model group, and the difference was statistically significant (p Emilia Sonchifolia group, Coptidis Rhizoma group and combined group were all effective in reducing the area of oral ulcer, among which the combined group was more effective. The level of pro-inflammatory factor TNF-α was reduced and the level of anti-inflammatory factor IL-2 was increased in the Emilia Sonchifolia group, Coptidis Rhizoma group and combined group, and the difference was statistically significant (p Conclusion: The combination of Coptidis Rhizoma and Emilia Sonchifolia is effective in the treatment of oral ulcer in rats, and the effect of the combination is better than that of the drug alone.

New therapy for oral ulcer:Evodia rutaecarpa patch combined with acupoint application

Background:Oral ulcer is the most common and easily recurrent disease in stomatology,which influence the patients’communication,normal dietary,and sleep.Evodia rutaecarpa(ER)is a traditional Chinese herbal medicine recorded in ancient Chinese medical books,which has a medicinal history of more than 2,000 years.Clinically,the application of ER at plantar Yongquan point(KI1)is effective in the treatment of oral ulcer.The purpose of this study was to combine the modern transdermal drug delivery system with traditional Chinese medicine to develop the transdermal absorption patch of ER and apply it to the treatment of oral ulcer at Yongquan point of plantar.Methods:Firstly,the medicinal materials of ER were extracted and the extracted materials were prepared into dispersed ER patch.The formulation and preparation process were screened by orthogonal design method and single factor investigation method.The adhesive and transdermal properties of the patch were used as the evaluation index of the preparation.Secondly,Wistar rats were used as experimental animals to establish a rat model of mouth ulcers.Wistar rats were randomly divided into normal group,model group(A),model group(B),low dose group,medium dose group and high dose group.the efficacy of ER on rat’s oral ulcer model was evaluated through three aspect such as apparent index,pathological index and biochemical index.Results:The patch had suitable adhesion and good skin penetration,which was an effective treatment for oral ulcer.In vivo pharmacodynamic studies,compared with the normal group,the body mass and food intake of rats in each group after modeling decreased,the amount of drinking water increased,the tissue structure of oral mucosa was damaged,and the levels of inflammatory factors(TNF-α,IL-6)and malondialdehyde increased,the levels of anti-inflammatory factors(IL-10),cell growth factor(epidermal growth factor,TGF-β_(1))and superoxide dismutase decreased.Compared with the model group,the body weight and food intake of each dosing group increased,water consumption decreased,the oral mucosal tissue structure was more complete,the levels of TNF-α,IL-6 and malondialdehyde decreased,the levels of IL-10,epidermal growth factor,TGF-β1 and superoxide dismutase increased,and the changes of various indexes were dose-related.Conclusion:ER patch can inhibit inflammatory reaction,enhance the antioxidant defense ability of the body,and promote the repair of damaged oral mucosa,so as to play an effective role in the treatment of oral ulcer.

Research Progress of Action Mechanism of Mongolian Medicine Hatageqi-7 in the Treatment of Recurrent Aphthous Ulcer

Based on Mongolian medical theory and modern pharmacology,literature on the main components and action mechanism of Hatageqi-7 in the treatment of recurrent aphthous ulcer is collected,sorted and summarized.The research hopes to provide certain basis for its clinical efficacy from theory.

Effect and mechanism of persimmon leaf flavonoid treatment of experimental oral ulcer

OBJECTIVE To explore the therapeutic effect and its mechanism of persimmon leaf flavonoids(PLF) on rats with oral ulcer. METHODS The oral ulcer model was induced by acetic acid,was used for intervention of Guilin watermelon frost and different dose(20,40 and 80 mg·kg^(-1)) of PLF.Ulcer area was calculated on the fourth and the seventh day after injury; the changes of superoxide dismutase(SOD) and malondialdehyde(MDA) in serum and ulcer tissues were observed; the level of tumor necrosis factor alpha(TNF-alpha) in ulcer tissue was measured. To observe the pathological morphological changes of H-E staining. RESULTS Guilin watermelon frost and PLF(40 and 80 mg·kg^(-1))can reduce the ulcer area(P<0.05); PLF(20,40 and 80 mg·kg^(-1)) can increase the activity of SOD and decrease the content of MDA in serum and ulcer tissue(P<0.05); Guilin watermelon frost and PLF could significantly decrease the levels of TNF-alpha in ulcer tissue(P<0.05),and improve the inflammatory infiltration of ulcer tissue. CONCLUSION PLF has certain therapeutic effects on oral ulcer induced by acetic acid,and the mechanism may be related to improve oxidative damage and reduce inflammatory reaction.

Therapeutic Evaluation of Recurrent Aphthous Ulcer with Integrated Traditional Chinese Medicine and Western Medicine

Objective: To observe the curative effects of Yiqing granule and Zhibai Dihuang pill combined with Oralpolin gel on recurrent aphthous ulcer. Methods: 150 patients with mild recurrent aphthous ulcer were classified as excessive internal heat type and deficiency internal heat type by traditional Chinese medicine theory. Then, they were randomly divided into the positive control group (thalidomide group), the trial group (Yiqing granule group/Zhibai Dihuang pill group), and the negative control group (topical medication group). All the patients in every group used Oralpolin gel. Additionally, the patients in the positive control group took thalidomide tablets orally and those in the trial group orally took proprietary Chinese medicine (Yiqing granule/Zhibai Dihuang pill). The treatment lasted for 4 weeks. The curative effects were all evaluated according to the “RAU Efficacy Evaluation Trial Standard” which was formulated by the Professional Committee of Mucosal Diseases of Chinese Stomatological Association. Results: Of all the 150 patients involved in this medical experiment, 146 cases finished it, including 66 ones in the trial group, 36 ones in the positive control group, and 44 ones in the negative control group. The total drop-out rate was 2.7%. For the excessive internal heat type, the effective rates in the thalidomide group, the Yiqing granule group and the local medication group were 91.7%, 52.6% and 52.9% respectively in order. For the deficiency internal heat type, the effective rates in the thalidomide group, the Zhibai Dihuang pill group and the local medication group were 87.5%, 71.4% and 40% respectively in order. The clinical efficacy of the Zhibai Dihuang pill group was better than that of the local medication group and similar to that of the thalidomide group (P Conclusion: Zhibai Dihuang pill is significantly effective in the treatment for mild recurrent aphthous ulcer of deficiency internal heat type without severe adverse reactions.

Treatment of oral ulcer based on TCM syndrome differentiation

Oral ulcer is a kind of ulcerative injury that occurs in the oral mucosa and is very common in clinic.In severe case,it can affect the quality of life of the patients.Western medicine treatment of oral ulcer is often prone to relapse,while the effect of traditional Chinese medicine treatment is remarkable.

RADIOIMMUNOASSAY OF SERUM FERRITIN LEVEL IN PATIENTS WITH RECURRENT APHTHOUS ULCERATION

The purpose of this study was to assess the correlation between iron deficiency and recurrent aphthous ulceration (RAU). Radioimmunoassay was used to examine the serum ferritin level (SFL) in 52 patients with RAU and in 54 controls. Both were divided into 2 groups in accordance with sex. The 36 female patients were subdivided into 3 age-groups as follows: 8 aged 22-24, 10 aged 25-34, and 18 aged 35-50 while the male patients were gathered as one single group aged 26-57. The subdivision was adapted similarly for the normal age-grouts. Although no significant difference in SFL was found between the male control and the male patient groups, differences between the female control and female patient groups showed highly significant which levels, with the ascendance of age, were P【0.001, P【0.005 and P【0.001, respectively. Also the difference between male and female control groups were significant (P【0.05). However, no significant differences in SFL were discovered among the 3 patient groups. 10 female patients with SFL【12ng/ml were tested with ferrous sulfate for one month, then their SFL was reexamined one week after the treatment. A highly significant difference in SFL was noted between the pre-ad post-treatment (P【0.001). 9 of them showed that the interval of recurrences were prolonged, the number of ulcers reduced, the pain less intensive and its duration shorter than those before the treatment. This study demonstrated that a singificant decrease in iron-storage occurred in female RAU patients. The authors concluded that the decrease SFL was possibly related to menstruation and child bearing.

Treatment of Oral Ulcer based on TCM Syndrome Differentiation

Oral ulcer is a kind of ulcerative injury that occurs in the oral mucosa and is very common in clinic.In severe case,it can affect the quality of life of the patients.Western medicine treatment of oral ulcer is often prone to relapse,while the effect of traditional Chinese medicine treatment is remarkable.

Fresh Amniotic Membrane Transplantation Combined Lamellar Keratoplasty for Patients with Recurrent Mooren's Ulcer

Purpose: To investigate the possibility of amniotic membrane as an immunologicalinsulating band to reduce the recurrent frequency of Mooren's ulcer.Methods: Twelve cases(12 eyes)with recurrent Mooren's Ulcer were observed. Amongthem, 4 cases(4 eyes)were male and 8 cases(8 eyes) female, ranging in age between 26and 51 years[mean(41 ± 3)years]. Three eyes recurred once, 5 eyes twice, and 4 eyesthree before. Eleven of 12 cases (11/12 eyes)with frequently recurrent Mooren's ulcerunderwent lamellar keratoplasty combined amniotic membrane transplantation(AMT).One patient who had entire corneal ulceration accepted AMT alone.Results: Follow-up time is 12 to 29 months, [mean (23 ± 6) months]. Before AMT, therecurrent frequency of Mooren's Ulcer of all cases after corneal surgery was 1 ～ 7 months[mean(3 ± 2)months]. Nine of 12 eyes with lamellar keratoplasty combined AMT did notrecur within the observation period; 2 eyes recurred 11 months after the surgery. Threemonths postoperatively, neovascularization was observed, which made it nearly impossibleto decipher between amniotic membrane and its nearby conjunctiva, only at the junctionof the transplant can some trails be observed. One case with entire AMT alone showedgraft resolution and neovascularization in 1 month.Conclusion:AMT combined with lamellar keratoplasty and lesion excision may delayrecurrence of Mooren's Ulcer, reduce its recurrent frequency. Besides the effects ofdecreasing inflammation, it may have immunological insulating function as well. Thisconclusion should be proven by further clinical comparative study of much moresamples.

Oral ulcerations as the first manifestations of acute leukemia: A case report

Acute myeloblastic leukemia (AML) is a highly fatal malignant bone marrow disease. Physicians, dentists and all other healthcare professionals should be aware of sinister oral signs and symptoms in order to early diagnosis and referral of patients. Here we report a case of AML who presented with oral ulcers. Ulcers developed after a parrot bite, which initially misled the physicians. Unfortunately our patient did not survive, but early diagnosis and prompt investigation and treatment can be life-saving in many other similar cases.

Role of colectomy in preventing recurrent primary sclerosing cholangitis in liver transplant recipients

AIM To study the published evidence on the impact of colectomy in preventing recurrent primary sclerosing cholangitis(r PSC). METHODS An unrestricted systematic literature search in Pub Med, EMBASE, Medline Ovid SP, ISI Web of Science, Lista(EBSCO) and the Cochrane library was performed on clinical studies investigating colectomy in liver transplantation(LT) recipients with and without r PSC in the liver allograft. Study quality was evaluated according to a modification of the methodological index for non-randomized studies(MINORS) criteria. Primary endpoints were the impact of presence, timing and type of colectomy on r PSC. Overall presence of inflammatory bowel disease(IBD), time of IBD diagnosis, posttransplant IBD and immunosuppressive regimen were investigated as secondary outcome.RESULTS The literature search yielded a total of 180 publications. No randomized controlled trial was identified. Six retrospective studies met the inclusion criteria of which 5 studies were graded as high quality articles. Reporting of IBD was heterogenous but in four publications, either inflammatory bowel disease, ulcerative colitis or in particular active colitis post-LT significantly increased the risk of r PSC. The presence of an intact(i.e., retained) colon at LT was identified as risk factor for r PSC in two of the high quality studies while four studies found no effect. Type of colectomy was not associated with r PSC but this endpoint was underreported(only in 33% of included studies).Neither tacrolimus nor cyclosporine A yielded a significant benefit in disease recurrence of primary sclerosing cholangitis(PSC).CONCLUSION The data favours a protective role of pre-/peri-LT colectomy in r PSC but the current evidence is not strong enough to recommend routine colectomy for r PSC prevention.

Complex reconstructive surgery for a recurrent ischial pressure ulcer with contralateral muscle

The management of recurrent pressure ulcers is a frequent problem in patients with spinal cord injuries. Many local muscle and fasciocutaneous flaps can be used to cover ulcers of all sizes. However, when a recurrent pressure ulcer has been repeatedly addressed, the number of available flaps becomes quite limited. Contralateral muscles, such as the gracilis, can be used to cover recurrent ischioperineal ulcers and should be employed before last resort surgeries, such as hip disarticulation and the total thigh flap.

Novel oral-targeted therapies for mucosal healing in ulcerative colitis

Ulcerative colitis(UC), a chronic, relapsing, remitting disease of the colon and rectum, is characterized by inflammatory ulceration of the mucosa. Current UC therapy relies on controlling acute episodes and preventing relapse. To predict modifications in the natural course of UC, mucosal healing(MH) has emerged as a major treatment goal. Endoscopic evaluation is considered the gold standard for assessing MH, which can be achieved by conventional drugs and biologics in many, but not all, patients. Consequently, interest is focusing on the development of new substances for UC therapy, and new oral agents are in the pipeline. This review will focus on the ability of newly developed oral drugs to induce and maintain MH in UC patients.

Formulation of a new phenytoin-containing mucoadhesive and evaluation of its healing effects on oral biopsy ulcers

Background and Objective: Several studies have shown the wound healing effect of topical phenytoin, which is applied by its effect on connective tissue intracellular matrix. However, there are still some controversies about its effect on various kinds of wounds, especially in the experimental models. This study is aimed at evaluating the effect of mucoadhesive paste compared to phenytoin mucoadhesive paste on wound healing after oral biopsy. Material and Methods: In this double blind randomized clinical trial, 20 patients who were eligible for oral biopsy were allocated into the case and control groups. After the biopsy, patients having ulcers ranging between one and two centimeters were treated by simple or 1% phenytoin mucoadhesive paste. All patients were instructed to apply their paste at least three times a day for five days after the biopsy. Patients in both groups were evaluated every other day for size of the ulcer, degree of pain and diameter of the inflammatory halo. Statistical analysis was done using SPSS software and Mann-Whitney test. Results: After the second and third appointments, it was observed that the rate of wound healing and decrease in the size of the ulcers were significantly quicker in the treatment group (p = 0.001 and p = 0.003 respectively) and the patients in the phenytoin group reported less pain. Diameter of the inflammatory halo was not significantly different between two groups. Conclusion: Applying 1% phenytoin mucoadhesive paste on biopsy ulcers resulted in accelerated wound healing and decrease in pain, but had no effect on the diameter of the inflammatory halo.

A head to head comparison of oral vs intravenous omeprazole for patients with bleeding peptic ulcers with a clean base,flat spots and adherent clots

AIM: To compare the effect of intravenous and oral omeprazole in patients with bleeding peptic ulcers with- out high-risk stigmata. METHODS: This randomized study included 211 pa- tients [112 receiving iv omeprazole protocol (Group 1), 99 receiving po omeprazole 40 mg every 12 h (Group 2)] with a mean age of 52.7. In 144 patients the ulcers showed a clean base, and in 46 the ulcers showed flat spots and in 21 old adherent clots. The endpoints were re-bleeding, surgery, hospital stay, blood transfusion and death. After discharge, re-bleeding and death were re- evaluated within 30 d. RESULTS: The study groups were similar with respect to baseline characteristics. Re-bleeding was recorded in 5 patients of Group 1 and in 4 patients of Group 2 (P = 0.879). Three patients in Group 1 and 2 in Group 2 underwent surgery (P = 0.773). The mean length of hospital stay was 4.6 ± 1.6 d in Group 1 vs 4.5 ± 2.6 d in Group 2 (P = 0.710); the mean amounts of blood transfusion were 1.9 ± 1.1 units in Group 1 vs 2.1 ± 1.7 units in Group 2 (P = 0.350). Four patients, two in each group died (P = 0.981). After discharge, a new bleed- ing occurred in 2 patients of Group 1 and in 1 patient of Group 2, and one patient from Group 1 died. CONCLUSION: We demonstrate that the effect of oral omeprazole is as effective as intravenous therapy in terms of re-bleeding, surgery, transfusion requirements, hospitalization and mortality in patients with bleeding ulcers with low risk stigmata. These patients can be treated effectively with oral omeprazole.

Combined chemo-endocrine therapy as a potential new option for HR+/HER2−advanced breast cancer:a prospective study of fulvestrant plus oral vinorelbine

Objective:Endocrine therapy with fulvestrant has shown synergistic antitumor effects with some chemotherapy drugs in vitro.This study evaluated the efficacy and safety of fulvestrant with vinorelbine in patients with hormone receptor positive(HR+)/human epidermal growth factor receptor-2-negative(HER2−)recurrent or metastatic breast cancer.Methods:Patients were intramuscularly administered fulvestrant 500 mg(day 1 per cycle for 28 days)and oral vinorelbine(60 mg/m2 on days 1,8,and 15 of each cycle).The primary endpoint was progression-free survival(PFS).Secondary endpoints included overall survival,objective response rate,disease control rate,duration of response,and safety.Results:A total of 38 patients with HR+/HER2−advanced breast cancer included in the study were followed up for a median time of 25.1 months.The overall median PFS was 9.86 months[95%confidence interval(CI)7.2-23.13],and the median PFS of the first-line and the second-line treatment population was 20.73 months(95%CI 9.82 to NR)and 4.27 months(95%CI 3.68 to NR),respectively.Most adverse events reported were of grade 1/2,and none were of grade 4/5.Conclusions:This is the first exploratory study of a fulvestrant and oral vinorelbine regimen in the treatment of HR+/HER2−recurrent and metastatic breast cancer.The combination chemo-endocrine therapy was efficacious,safe,and promising for patients with HR+/HER2−advanced breast cancer.

Combination of Diclofenac Potassium and Propolis in the Therapy of Oral Aphthosis: A Randomized, Clinical, Double-Blind, Placebo-Controlled Study

Background: Oral aphthosis has a negative impact on oral health. This study aimed to assess the effectiveness of gel formulation including diclofenac and propolis in the treatment of oral ulcers. Methods: Participants included 100 normal individuals with aphthous, excluding those having allergies to any ingredient in the diclofenac formulation. Patients were randomly assigned into two groups: one group received treatment with a combination of diclofenac potassium 3% (10 mg/g, 60 g) and propolis 5% gel (Group II), and the other group received a placebo (Group 1). The patient was evaluated using standard digital photographs and chronic oral mucosal questionnaires on days 1, 3, 5, and 7 after healing. Utilizing the Mann-Whitney U test, the two groups were compared. Each group’s changes were examined using Friedman’s test. Results: There was a statistically dramatic change over time in Group II. After one day, the median total score dropped statistically significantly, and from one to three days with effect size (d) 2.485, Group II demonstrated 48% complete healing and 52% partial healing, while Group I demonstrated 4% partial healing and 96% no change. Effect size (V): 0.995. Conclusions: The combination of diclofenac and propolis provided instant relief and an affordable new regimen for treating oral aphthosis.